Background:
Prostaglandin E2 (
PGE2) induces
aromatase expression in adipose tissue, leading to increased
estrogen production that may promote the development and progression of
breast cancer. However, few studies have simultaneously investigated systemic levels of
PGE2 and
estrogen in relation to postmenopausal
breast cancer risk.Methods: Here, we determined urinary
estrogen metabolites (EM) using mass spectrometry in a case-cohort study (295 incident
breast cancer cases and 294 subcohort members), and using linear regression estimated the effect of urinary levels of a major
PGE2 metabolite (
PGE-M) on EMs. HRs for the risk of developing
breast cancer in relation to
PGE-M and EMs were compared between Cox regression models with and without mutual adjustment.Results:
PGE-M was a significant predictor of
estrone (E1), but not
estradiol (E2) levels in multivariable analysis. Elevated E2 levels were associated with an increased risk of developing
breast cancer [HRQ5vs.Q1, 1.54; 95% confidence interval (CI), 1.01-2.35], and this association remained unchanged after adjustment for
PGE-M (HRQ5vs.Q1, 1.52; 95% CI, 0.99-2.33). Similarly, elevated levels of
PGE-M were associated with increased risk of developing
breast cancer (HRQ4vs.Q1, 2.01; 95% CI, 1.01-4.29), and this association was only nominally changed after consideration of E1 or E2 levels.Conclusions: Urinary levels of
PGE-M and
estrogens were independently associated with future risk of developing
breast cancer among these postmenopausal women.Impact: Increased
breast cancer risk associated with
PGE-M might not be fully explained by the
estrogens-
breast cancer association alone but also by additional effects related to
inflammation.
Cancer Epidemiol
Biomarkers Prev; 26(3); 383-8. ©2016 AACR.